Biomedical subjects
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Precipitation is the primary water resource. Equal attention should be given to the management of evapotranspiration, surface and ground water as well as water storage.
The objective of this prospective study was to compare the outcome of ovarian hyperstimulation for in-vitro fertilization (IVF) using two different preparations of recombinant follicle stimulating hormone (FSH). The study was based on 296 consecutive IVF cycles in 1997, 199 performed using follitropin alpha (Gonal-F) and 97 performed using follitropin beta (Puregon). Outcome was compared regarding pregnancy rate, oestradiol and progesterone response, endometrial thickness, follicle number, number of retrieved oocytes, fertilized oocytes, sperm count and sperm motility. There was no significant difference in outcome of stimulation. Clinical pregnancy rate was similar, 29.1% for Gonal-F and 28.1% for Puregon. There was no difference in endometrial response, oestradiol response, number of smaller (12-15 mm) or larger (>15 mm) follicles, number of oocytes retrieved, fertilized, divided and replaced, in sperm counts or in sperm progressive motility. There was a lower follicle number in the Puregon group, but not statistically significant. The serum progesterone concentrations on the day of oocyte retrieval, however, were significantly lower in the Puregon group. In conclusion, it was not possible to find significant differences in the IVF programme with regard to stimulation outcome between Gonal-F and Puregon. The results of this study indicate that Gonal-F and Puregon may be equally suitable for use in ovarian stimulation for IVF.
OBJECTIVE: To study increases of serum FSH and gonadal response in gonadotropin-deficient men treated with recombinant FSH (Puregon; NV Organon, Oss, The Netherlands). DESIGN: An open, prospective, multiple rising dose study in which volunteers received single daily IM doses of recombinant FSH for 3 weeks. The dose administered was increased at weekly intervals: the first 7 days, 75 IU/d; the subsequent 7 days, 150 IU/d; and the last 7 days, 225 IU/d. PARTICIPANTS: Nine men suffering from isolated gonadotropin deficiency or panhypopituitarism. MAIN OUTCOME MEASUREMENTS: Immunoreactive FSH, LH, inhibin, T, and androstenedione. RESULTS: Serum immunoreactive FSH (median) rose in accordance with the recombinant FSH doses administered from 0.5 mIU/mL (range < 0.05 to 1.9 mIU/mL) at baseline to 4.3 mIU/mL (range 2.0 to 8.5 mIU/mL), 8.4 mIU/mL (range 4.9 to 17.8 mIU/mL), and 13.6 mIU/mL (5.6 to 28.4 mIU/mL) after 1, 2, and 3 weeks of medication, respectively. The elimination half-life of recombinant FSH was 48 +/- 5 hours (mean +/- SD), which was slightly longer than that reported after single dose administration of recombinant FSH (32 +/- 12 hours). The bioactivity of recombinant FSH was reflected by serum inhibin levels, which rose from 116 U/L (range 34 to 356 U/L) at baseline to 350 U/L (range 63 to 1,109 U/L) at day 22. However, serum FSH and inhibin levels did not correlate when compared after 1, 2, and 3 weeks of recombinant FSH administration. Serum immunoreactive LH, T, androstenedione, and E2 were 0.2 mIU/mL (range < 0.05 to 0.7 mIU/mL [conversion factor to SI unit, 1.0]), 58 ng/dL (range < 12 to 222 ng/dL [conversion factor to SI unit, 0.0347]), 14 ng/dL (range 6 to 115 ng/dL [conversion factor to SI unit, 0.0349]), and 14 pg/mL (range < 14 to 16 pg/mL [conversion factor to SI unit, 3.67]), respectively, at baseline and remained unchanged during the entire treatment period. CONCLUSION: These data indicate that recombinant FSH treatment increases serum FSH in a dose-proportional fashion, increases inhibin secretion, and lacks intrinsic LH activity.
We have examined the efficacy of highly purified follicle stimulating hormone (FSH-HP) for controlled ovarian stimulation in our in-vitro fertilization (IVF) programme, and compared the results obtained with this preparation with those using human menopausal gonadotrophin (HMG) in 15 patients who had received treatment with both FSH-HP and HMG in consecutive cycles (n = 39). No differences were found in the duration of stimulation, which was 13.9 days (HMG) as compared with 14.3 days (FSH-HP). However, in the FSH-HP-treated cycles we found a striking difference in the rise of serum oestradiol, which was significantly lower than in HMG-treated cycles (2953 +/- 938 pmol/l as compared with 6349 +/- 3683 pmol/l on the day before ovum retrieval). Number and size of follicles were similar in the two groups, as were oocyte characteristics. Increase in endometrial thickness at two days prior to ovum retrieval was slightly higher after HMG. The results indicate that in combination with a long gonadotrophin-releasing hormone agonist (GnRHa) protocol, pure FSH is sufficient for adequate follicle recruitment and growth. However, since FSH-HP resulted in markedly reduced concentrations of serum oestradiol as compared to HMG cycles, IVF programmes using repeated oestradiol measurements to decide the day of ovum retrieval must take this into consideration in order not to prolong the stimulation unnecessarily.
Seven women suffering from hypogonadism due to previous hypophysectomy, isolated gonadotrophin deficiency, or Kallman's syndrome [median age 39 years (range 24-45)] volunteered to participate in a study to assess ovarian response following multiple-dose administration of recombinant human follicle-stimulating hormone (rhFSH; Org 32489). Baseline serum FSH and luteinizing hormone (LH) concentrations were 0.25 (< 0.05-1.15) IU/l and 0.06 (< 0.05-0.37) IU/l, respectively. Subjects received daily i.m. injections of rhFSH for 3 weeks (week 1: 75 IU/day, week 2: 150 IU/day, week 3: 225 IU/day). Blood sampling and sonographic investigations were performed on alternate days. Steady-state FSH concentrations were reached approximately 3-5 days after alterations of the doses administered. Maximum FSH concentrations were between 7.1 and 11.8 IU/l, whereas serum LH concentrations remained unchanged. Due to absent follicle development and lack of a rise in immunoreactive inhibin (INH) (response failure possibly due to early ovarian failure or resistant ovary syndrome) in two subjects, analysis of ovarian response was restricted to five volunteers. Serum androstenedione levels showed no significant changes during rhFSH administration. Although serum immunoreactive INH concentrations reached normal late follicular values [659 (388-993) IU/l], serum oestradiol revealed only a minor increase [77 (18-210) pmol/l]. Moreover, growth of (multiple) ovarian follicles was observed up to pre-ovulatory sizes (> 15 mm) in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To assess safety, pharmacokinetic, and pharmacodynamic properties of recombinant human follicle-stimulating hormone (FSH; Org 32489, Organon International, Oss, The Netherlands) after a single intramuscular injection in the buttock. DESIGN: In a prospective study, safety variables, serum FSH, luteinizing hormone, inhibin, estradiol (females only), and testosterone (males only) were evaluated up to a maximum of 11 days after injection of 300 IU recombinant FSH. SETTING: Four specialist Reproductive Endocrinology and Infertility units. VOLUNTEERS: Fifteen men and women exhibiting all pituitary gonadotropin deficiency. RESULTS: A single bolus of 300 IU recombinant FSH was well tolerated, and no drug-related adverse effects were noted. Comparison of before and after treatment safety variables, including serum antirecombinant FSH antibodies, showed no changes of clinical relevance. Analysis of serum FSH levels revealed comparable elimination half-lives of 44 +/- 14 (mean +/- SD) and 32 +/- 12 hours in women and men volunteers, respectively. In contrast, peak FSH concentrations were significantly lower in women than in men volunteers (4.3 +/- 1.7 versus 7.4 +/- 2.8 IU/L), and the time required to reach peak levels of FSH was significantly longer in women than in men (27 +/- 5 versus 14 +/- 8 hours). The area under the serum level versus time curve tended to be smaller in women than in men volunteers (339 +/- 105 versus 452 +/- 183 IU/L x hours), but the difference did not reach statistical significance. Together these data suggest that recombinant FSH is absorbed from its intramuscular depot to a lower rate and extent in women than in men. In both sexes a relationship between serum FSH levels and body weight was apparent. During the experimental period, other hormones remained low at baseline levels or were only slightly increased. CONCLUSION: Our findings indicate that recombinant FSH is well tolerated and that it is absorbed from its intramuscular depot to a higher rate and extent in men than in women. After intramuscular administration, its half-life is in good agreement with that previously reported for natural FSH.
Using a randomized, cross-over design, the clinical, pharmacokinetic and pharmacodynamic properties of commercially available gonadotrophin preparations were studied. Following i.v. administration of 150 IU of follicle-stimulating hormone (FSH) in the form of Humegon, Pergonal and Metrodin, the maximum concentrations (CMax) were 27.5, 24.1 and 26.5 IU/l, respectively which were reached after 15.4, 16.9 and 16.9 min (TMax), respectively. The half lives (t1/2) were 1.6, 2.3 and 2.0 h, respectively (fast compartment) and 11, 10 and 7.3 h, respectively (slow compartment). The t1/2 of luteinizing hormone (LH) could only be estimated in a surgically hypophysectomized patient: the fast compartment was 1.2 and 1.3 h after the administration of Humegon and Pergonal, respectively and the slow compartment was 3.3 h in both cases. Marked individual differences of the same type were found in plasma FSH profiles, ovarian images and peripheral oestradiol levels after the administration of both preparations (150 IU daily for 8 days) and the approximate t1/2 of FSH exceeded 40 h. It is concluded that the pharmacokinetic and pharmacodynamic properties of the preparations studied are similar, if not identical, and that there are marked individual differences in patient responsiveness, which are unrelated to the preparation administered.
The biologic (B) and immunologic (I) properties of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in three commercial urinary gonadotropin preparations and in the first international standard preparation of human urinary gonadotropins before and after fractionation by isoelectrofocusing (IEF). Significant differences were found in the IEF profiles of both bioactive and immunoreactive LH and FSH and in the B/I ratios of the preparations studied. The observed differences in the molecular composition of LH and FSH seem to be attributable to the purification procedures employed. The possible influence of these differences on the in vivo potencies, circulating half-lives, and clinical effects of gonadotropin preparations are discussed.
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Fifteen patients underwent first-trimester abortion by one of two techniques. In group P, seven patients received prostaglandin vaginal suppositories during the 12 hours prior to vacuum aspiration, whereas eight patients in group V were aborted by aspiration alone. During the first postabortion menstrual cycle, daily peripheral blood levels of several hormones, including follicle-stimulating hormone (FSH), luteinizing hormone, human chorionic gonadotropin, estradiol, and progesterone, were determined. Patients in group P demonstrated a more rapid fall in progesterone levels following pregnancy termination (P less than 0.01). They also experienced a more physiologic first postabortion cycle as evidenced by a larger preovulatory estradiol peak (P less than 0.05) and a more normal luteal phase as judged by both the duration and elevation of progesterone levels. Certain endocrine changes common to both groups but different from those of normally menstruating women were also observed. These consisted of short-term spurts of progesterone secretion in many patients (10 of 15) prior to ovulation and exaggerated levels of FSH during the early follicular phase.
The cervical bacterial flora in early pregnancy, labour, and infertility was assessed qualitatively. The cervix harboured several types of bacteria in both pregnant and infertile women. In the latter group, however, fewer species were found. The incidence of a mixed aerobic and anaerobic flora differed significantly between patient categories as did the frequency with which only aerobic isolates were obtained. There was also a significant difference between patient groups with regard to the incidence of anaerobic isolates. Among the anaerobic bacteria, peptostreptococci and bacteroides species were the dominating ones whereas coagulase-negative staphylococci were the most prevalent aerobic bacteria. Lactobacilli constituted 29--44% of the anaerobic bacteria found in the pregnant cervix and 52% of those found in the infertile cervix. The distribution of different aerobes as well as anaerobes was similar in pregnant and infertile patients.
With the aim to find criteria for the prediction of the patients who are at risk of developing a post-abortion infection the pretreatment cervical microbial flora was compared between one series of patients who developed and another series of patients who did not develop such an infection. Aerobic and anaerobic bacteria as well as mycoplasma and fungi, were studied in 104 patients. The distribution of aerobic and anaerobic bacteria was similar in the 14 patients who later developed post-abortal infection and in uncomplicated cases. It is concluded that the cultivation of the cervical microbial flora cannot serve as a basis for the prediction of which patients will develop subsequent genital infections.